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1.
Eur J Pharm Sci ; 202: 106896, 2024 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-39250981

RESUMO

Recent advances in understanding Alzheimer's disease (AD) suggest the possibility of an infectious etiology, with Porphyromonas gingivalis emerging as a prime suspect in contributing to AD. P. gingivalis may invade systemic circulation via weakened oral/intestinal barriers and then cross the blood-brain barrier (BBB), reaching the brain and precipitating AD pathology. Based on the proposed links between P. gingivalis and AD, a prospective approach is the development of an oral nanovaccine containing P. gingivalis antigens for mucosal delivery. Targeting the gut-associated lymphoid tissue (GALT), the nanovaccine may elicit both mucosal and systemic immunity, thereby hampering P. gingivalis ability to breach the oral/intestinal barriers and the BBB, respectively. The present study describes the optimization, characterization, and in vitro evaluation of a candidate chitosan-coated poly(lactic-co-glycolic acid) (PLGA-CS) nanovaccine containing a P. gingivalis antigen extract. The nanocarrier was prepared using the double emulsion solvent evaporation method and optimized for selected experimental factors, e.g. PLGA amount, surfactant concentration, w1/o phase ratio, applying a d-optimal statistical design to target the desired physicochemical criteria for its intended application. After nanocarrier optimization, the nanovaccine was characterized in terms of particle size, polydispersity index (PdI), ζ-potential, encapsulation efficiency (EE), drug loading (DL), morphology, and in vitro release profile, as well as for mucoadhesivity, stability under simulated gastrointestinal conditions, antigen integrity, in vitro cytotoxicity and uptake using THP-1 macrophages. The candidate PLGA-CS nanovaccine demonstrated appropriate physicochemical, mucoadhesive, and antigen release properties for oral delivery, along with acceptable levels of EE (55.3 ± 3.5 %) and DL (1.84 ± 0.12 %). The integrity of the encapsulated antigens remained uncompromised throughout NPs production and simulated gastrointestinal exposure, as confirmed by SDS-PAGE and Western blotting analyses. Furthermore, the nanovaccine showed effective in vitro uptake, while exhibiting low cytotoxicity. Taken together, these findings underscore the potential of PLGA-CS NPs as carriers for adequate antigen mucosal delivery, paving the way for further investigations into their applicability as vaccine candidates against P. gingivalis.


Assuntos
Antígenos de Bactérias , Quitosana , Portadores de Fármacos , Nanopartículas , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Porphyromonas gingivalis , Quitosana/química , Quitosana/administração & dosagem , Porphyromonas gingivalis/efeitos dos fármacos , Humanos , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Portadores de Fármacos/química , Nanopartículas/administração & dosagem , Antígenos de Bactérias/administração & dosagem , Antígenos de Bactérias/imunologia , Vacinas Bacterianas/administração & dosagem , Vacinas Bacterianas/imunologia , Liberação Controlada de Fármacos
2.
Crit Rev Oncol Hematol ; 204: 104505, 2024 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-39255911

RESUMO

Biliary tract cancers (BTCs) are aggressive malignancies with a dismal prognosis that require intensive targeted therapy. Approximately 10 % of BTCs have PBRM1 mutations, which impede DNA damage repair pathways and make cancer cells more susceptible to DNA-damaging chemicals. This review focus on development of poly(lactic-co-glycolic acid) (PLGA)-based nanoparticles targeting delivery system to selectively deliver chemotherapy into PBRM1-deficient BTC cells. These nanoparticles improve therapy efficacy by increasing medication targeting and retention at tumour locations. In preclinical studies, pharmacokinetic profile of this nanoparticle was encouraging and supported its ability to achieve extended circulation time with high drug accumulation in tumor. The review also highlights potential of Pou3F3:I54N to expedite bioassays for patient selection in BTC targeted therapies.

3.
Pathol Res Pract ; 263: 155629, 2024 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-39348749

RESUMO

Chronic obstructive pulmonary disease (COPD) is strongly linked to cigarette smoke, which contains toxins that induce oxidative stress and airway inflammation, ultimately leading to premature airway epithelial cell senescence and exacerbating COPD progression. Current treatments for COPD are symptomatic and hampered by limited efficacy and severe side effects. This highlights the need to search for an optimal therapeutic candidate to address the root causes of these conditions. This study investigates the possible potential of poly (lactic-co-glycolic acid) (PLGA)-based nanoparticles encapsulating the plant-based bioactive compound 18-ß-glycyrrhetinic acid (18ßGA) as a strategy to intervene in cigarette smoke extract (CSE)-induced oxidative stress, inflammation, and senescence, in vitro. We prepared 18ßGA-PLGA nanoparticles, and assessed their effects on cell viability, reactive oxygen species (ROS) production, anti-senescence properties (expression of senescence-associated ß galactosidase and p21 mRNA), and expression of pro-inflammatory genes (CXCL-1, IL-6, TNF-α) and inflammation-related proteins (IL-8, IL-15, RANTES, MIF). The highest non-toxic concentration of 18ßGA-PLGA nanoparticles to healthy human broncho epithelial cell line BCiNS1.1 was identified as 5 µM. These nanoparticles effectively mitigated cigarette smoke-induced inflammation, reduced ROS production, protected against cellular aging, and counteracted the effects of CSE on the expression of the inflammation-related genes and proteins. This study underscores the potential of 18ßGA encapsulated in PLGA nanoparticles as a promising therapeutic approach to alleviate cigarette smoke-induced oxidative stress, inflammation, and senescence. Further research is needed to explore the translational potential of these findings in clinical and in vivo settings.

4.
Nanotechnology ; 2024 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-39332438

RESUMO

Biomaterial-based implantable scaffolds capable of promoting physical and functional reconnection of injured spinal cord and nerves represent the latest frontier in neural tissue engineering. Here, we report the fabrication and characterization of self-standing, biocompatible and bioresorbable substrates endowed with both controlled nanotopography and electroactivity, intended for the design of transient implantable scaffolds for neural tissue engineering. In particular, we obtain conductive and nano-modulated poly(D,L-lactic acid) (PLA) and poly(lactic-co-glycolic acid) (PLGA) free-standing films by simply iterating a replica moulding process and coating the polymer with a thin layer of poly(3,4-ethylendioxythiophene) polystyrene sulfonate (PEDOT:PSS). The capability of the substrates to retain both surface patterning and electrical properties when exposed to a liquid environment has been evaluated by atomic force microscopy, electrochemical impedance spectroscopy and thermal characterizations. In particular, we show that PLA-based films maintain their surface nano-modulation for up to three weeks of exposure to a liquid environment, a time sufficient for promoting axonal anisotropic sprouting and growth during neuronal cell differentiation. In conclusion, the developed substrates represent a novel and easily-tunable platform to design bioresorbable implantable devices featuring both topographic and electrical cues. .

5.
Hua Xi Kou Qiang Yi Xue Za Zhi ; 42(5): 572-580, 2024 Oct 01.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-39304501

RESUMO

OBJECTIVES: This study aimed to explore the effects of bone morphogenetic protein 2 (BMP-2) encapsula-ted in poly(lactic-co-glycolic acid) (PLGA) microcapsules with different molecular weights on the osteogenic ability of osteoblasts. METHODS: PLGA microcapsules with different molecular weights (12 000, 30 000) encapsulating BMP-2, were prepared using a dual-channel microinjection pump. The morphology and structure of the microcapsules were characterized by optical microscopy and scanning electron microscopy. The sustained-release performance of the microcapsules was characterized by phosphate buffered saline immersion method. The cell compatibility of the microcapsules was detected by the Calcein-AM/PI staining and CCK-8 method. The chemotactic effect of BMP-2-encapsulated microcapsules on MC3T3-E1 cells after 48 h of treatment was detected by the Transwell assay. The alkaline phosphatase activity assay and Alizarin Red S staining were used to characterize the effect of microcapsules on the osteogenic ability of MC3T3-E1 cells. RESULTS: Both types of microcapsules with different molecular weights exhibited smooth surfaces, as well as uniform and good cell compatibility. The chemotactic effect of the 12 000 microcapsules was outstanding. The 30 000 microcapsules had a longer sustained-release time, and the initial burst release was reduced by approximately 25% compared with the 12 000 microcapsules. In addition, 30 000 microcapsules performed better in long-term osteogenesis induction than 12 000 microcapsules. CONCLUSIONS: In this study, the release of BMP-2 is regulated by adjusting the molecular weight of PLGA, and the results indicate that 30 000 microcapsules can better induce the long-term osteogenic ability of MC3T3-E1 cells.


Assuntos
Proteína Morfogenética Óssea 2 , Cápsulas , Peso Molecular , Osteoblastos , Osteogênese , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Osteogênese/efeitos dos fármacos , Osteoblastos/efeitos dos fármacos , Animais , Camundongos , Fosfatase Alcalina/metabolismo , Diferenciação Celular , Ácido Poliglicólico , Ácido Láctico
6.
J Pharm Sci ; 2024 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-39218154

RESUMO

Erosion of biodegradable polymeric excipients, such as polylactic acid (PLA) and polylactic-co-glycolic acid (PLGA), is generally characterized by microbalance for the remaining mass of PLA and/or PLGA and Gel Permeation Chromatography (GPC) for molecular weight (MW) decrease. For polymer erosion studies of intravitreal sustained release brimonidine implants, however, both microbalance and GPC present several challenges. Mass loss measurement by microbalance does not have specificity for excipient polymers and drug substances. Accuracy of the remaining mass by weighing could also be low due to sample mass loss through retrieval-drying steps, especially at later drug release (DR) time points. When measuring the decrease of polymer MW by GPC, trace amounts of polymeric degradants (oligomers and/or monomers) trapped inside the implants during DR tests may not be measurable due to sensitivity limitations of the GPC detector and column MW range. Previous efforts to measure remained PLGA weight of dexamethasone micro-implants using qNMR with external calibration have been performed, however, these measurements do not account for chemical structure changes (i.e. LA to GA ratio changes from time zero) of PLGA implants during drug release tests. Here, a qNMR method with an internal standard was developed to monitor the following changes in micro-implants during drug release tests: 1. The remaining overall PLA/PLGA mass. 2. The remaining lactic acid (LA), glycolic acid (GA) unit and PLGA's lauryl ester end group percentages. 3. The trace content of PLA/PLGA oligomers as degradants retained in the implants. Unlike microbalance analysis, qNMR has both specificity for drug substance, excipient polymer, and accuracy due to minimal implant loss during sample preparation. Compared to the overall PLA/PLGA remaining mass generally monitored in erosion studies, the percentage of remaining LA, GA, and the ester end group provide more information about the microstructure change (such as hydrophobicity) of PLA/PLGA. Additionally, the qNMR method can complement GPC methods by measuring the change of remaining PLA and PLGA oligomer concentrations in brimonidine implants, with tenfold less sample and no MW cutoff. The qNMR method can be used as a sensitive tool for both polymer excipient characterization and kinetics studies of brimonidine implant erosion.

7.
J Biomater Appl ; : 8853282241281439, 2024 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-39264258

RESUMO

Large bone defect repair is a striking challenge in orthopedics. Currently, inorganic-organic composite scaffolds are considered as a promising approach to these bone regeneration. Silicon ions (Si4+) are bioactive and beneficial to bone regeneration and Si4+-containing inorganic mesoporous silica (MS) can effectively load drugs for bone repair. To better control the release of drug, we prepared biodegradable MS/PLGA (MP) microspheres. MP loaded organic silk fibroin/carboxymethyl chitosan/sodium alginate (MP/SF/CMCS/SA) composite scaffolds were further constructed by genipin and Ca2+ crosslinking. All MP/SF/CMCS/SA scaffolds had good swelling ability, degradation rate and high porosity. The incorporation of 1% MP significantly enhanced the compressive strength of composite scaffolds. Besides, MP loaded scaffold showed a sustained release of Si4+ and Ca2+. Moreover, the release rate of rhodamine (a model drug) of MP/SF/CMCS/SA scaffolds was obviously lower than that of MP. When culturing with rat bone marrow mesenchymal stem cells, scaffolds with 1% MP displayed good proliferation, adhesion and enhanced osteogenic differentiation ability. Based on the results above, the addition of 1% MP in SF/CMCS/SA scaffolds is a prospective way for drug release in bone regeneration and is promising for further in vivo bone repair applications.

8.
Spectrochim Acta A Mol Biomol Spectrosc ; 325: 125081, 2024 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-39241396

RESUMO

Theoretical MP2 and B3LYPD3 calculations, as well as experimental matrix isolation infrared spectroscopy studies, were used to investigate the 1:1 complexes formed between glycolic acid and water. Out of five computationally predicted forms of GA⋯H2O complex the most stable one was detected experimentally in solid argon. This structure is characterized by two intermolecular OH⋯O hydrogen bonds depicting a six-member ring in which water acts both as a proton acceptor and as a proton donor. Two other structures with the alcoholic OH group acting as a proton donor are also tentatively suggested to be present in solid argon.

9.
Int Immunopharmacol ; 141: 112883, 2024 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-39153305

RESUMO

Ectodermal mesenchymal stem cells-derived conditioned medium (EMSCs-CM) has been reported to protect against ulcerative colitis (UC) in mice, but its underlying mechanism in alleviating UC need to be further elucidated. Here, it is reported that EMSCs-CM could attenuate pro-inflammatory response of LPS-induced IEC-6 cells and regulate the polarization of macrophages towards anti-inflammatory type in vitro. Furthermore, PLGA microspheres prepared by the double emulsion method were constructed for oral delivery of EMSCs-CM (EMSCs-CM-PLGA), which are beneficial for colon-targeted adhesion of EMSCs-CM to the damaged colon mucosa. The results showed that orally-administered of EMSCs-CM-PLGA microspheres reduced inflammatory cells infiltration and maintained the intestinal mucosal barrier. Further investigation found that EMSCs-CM-PLGA microspheres treatment gradually inhibited the activation of NF-κB pathway to regulate M1/M2 polarization balance in colon tissue macrophages, thereby alleviating DSS-induced UC. These results of this study will provide a theoretical basis for clinical application of EMSCs-CM in UC repair.


Assuntos
Colite Ulcerativa , Macrófagos , Células-Tronco Mesenquimais , Microesferas , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Animais , Colite Ulcerativa/terapia , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/imunologia , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Meios de Cultivo Condicionados/farmacologia , Macrófagos/imunologia , Macrófagos/efeitos dos fármacos , Camundongos , Colo/patologia , Colo/efeitos dos fármacos , NF-kappa B/metabolismo , Sulfato de Dextrana , Masculino , Linhagem Celular , Mucosa Intestinal/patologia , Mucosa Intestinal/imunologia , Mucosa Intestinal/metabolismo , Mucosa Intestinal/efeitos dos fármacos , Modelos Animais de Doenças , Ratos , Anti-Inflamatórios/uso terapêutico , Anti-Inflamatórios/farmacologia , Camundongos Endogâmicos C57BL , Humanos
10.
Sheng Wu Gong Cheng Xue Bao ; 40(8): 2418-2431, 2024 Aug 25.
Artigo em Chinês | MEDLINE | ID: mdl-39174462

RESUMO

Glycolic acid is an important chemical product widely used in various fields, including cosmetics, detergents, textiles, and more. Currently, microbial production of glycolic acid has disadvantages such as poor genetic stability, low yield, and high cost. Additionally, whole-cell catalytic production of glycolic acid typically requires the addition of relatively expensive sorbitol as a carbon source, which limits its industrial production. To develop an industrially applicable method for glycolic acid production, this study used ethylene glycol as a substrate to screen the glycolic acid-producing strains through whole-cell catalysis, obtaining a Rhodotorula sp. capable of producing glycolic acid. The strain was then subjected to UV mutagenesis and high throughput screening, and the positive mutant strain RMGly-20 was obtained. After optimization in shake flasks, the glycolic acid titer of RMGly-20 reached 17.8 g/L, a 10.1-fold increase compared to the original strain. Using glucose as the carbon source and employing a fed-batch culture in a 5 L fermenter, strain RMGly-20 produced 61.1 g/L of the glycolic acid. This achievement marks the preliminary breeding of a genetically stable glycolic acid-producing strain using a cheap carbon source, providing a new host for the biosynthesis of glycolic acid and promoting further progress toward industrial production.


Assuntos
Fermentação , Glicolatos , Rhodotorula , Glicolatos/metabolismo , Rhodotorula/metabolismo , Rhodotorula/genética , Microbiologia Industrial/métodos , Etilenoglicol/metabolismo , Mutagênese
11.
FEMS Yeast Res ; 242024 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-39104224

RESUMO

Plastics have become an indispensable material in many fields of human activities, with production increasing every year; however, most of the plastic waste is still incinerated or landfilled, and only 10% of the new plastic is recycled even once. Among all plastics, polyethylene terephthalate (PET) is the most produced polyester worldwide; ethylene glycol (EG) is one of the two monomers released by the biorecycling of PET. While most research focuses on bacterial EG metabolism, this work reports the ability of Saccharomyces cerevisiae and nine other common laboratory yeast species not only to consume EG, but also to produce glycolic acid (GA) as the main by-product. A two-step bioconversion of EG to GA by S. cerevisiae was optimized by a design of experiment approach, obtaining 4.51 ± 0.12 g l-1 of GA with a conversion of 94.25 ± 1.74% from 6.21 ± 0.04 g l-1 EG. To improve the titer, screening of yeast biodiversity identified Scheffersomyces stipitis as the best GA producer, obtaining 23.79 ± 1.19 g l-1 of GA (yield 76.68%) in bioreactor fermentation, with a single-step bioprocess. Our findings contribute in laying the ground for EG upcycling strategies with yeasts.


Assuntos
Biodiversidade , Etilenoglicol , Fermentação , Glicolatos , Glicolatos/metabolismo , Etilenoglicol/metabolismo , Reatores Biológicos/microbiologia , Leveduras/metabolismo , Leveduras/genética , Saccharomyces cerevisiae/metabolismo , Saccharomyces cerevisiae/genética
12.
Kidney Int ; 2024 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-39197585

RESUMO

We recently reported the case of a patient who experienced three consecutive episodes of acute kidney injury, all of them following a "Brazilian" hair-straightening treatment. The cream used for the straightening procedure contained glyoxylic acid. To examine possible underlying mechanisms causing kidney injury, four groups of mice were exposed to topical application of (i) the straightening product, (ii) a cream containing 10% glyoxylic acid, (iii) a cream containing 10% glycolic acid or (iv) a control cream. Application of glycolic acid slightly increased urine oxalate excretion, while glyoxylic acid and the straightening product dramatically increased urine oxalate excretion and caused calcium oxalate nephropathy after transcutaneous absorption. Thus, glyoxylic acid was presumptively absorbed through the skin, metabolized to oxalate and promoted crystallization of calcium oxalate in urine. Hence, cosmetic products containing glyoxylic acid may induce acute kidney injury and should be discontinued. Further studies are needed to investigate the metabolism of glycolic acid and glyoxylic acid following topical application.

13.
Gels ; 10(8)2024 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-39195026

RESUMO

Poly(lactic-co-glycolic acid) (PLGA) hydrogels are highly utilized in biomedical research due to their biocompatibility, biodegradability, and other versatile properties. This review comprehensively explores their synthesis, properties, sustained release mechanisms, and applications in drug delivery. The introduction underscores the significance of PLGA hydrogels in addressing challenges like short half-lives and systemic toxicity in conventional drug formulations. Synthesis methods, including emulsion solvent evaporation, solvent casting, electrospinning, thermal gelation, and photopolymerization, are described in detail and their role in tailoring hydrogel properties for specific applications is highlighted. Sustained release mechanisms-such as diffusion-controlled, degradation-controlled, swelling-controlled, and combined systems-are analyzed alongside key kinetic models (zero-order, first-order, Higuchi, and Peppas models) for designing controlled drug delivery systems. Applications of PLGA hydrogels in drug delivery are discussed, highlighting their effectiveness in localized and sustained chemotherapy for cancer, as well as in the delivery of antibiotics and antimicrobials to combat infections. Challenges and future prospects in PLGA hydrogel research are discussed, with a focus on improving drug loading efficiency, improving release control mechanisms, and promoting clinical translation. In summary, PLGA hydrogels provide a promising platform for the sustained delivery of therapeutic agents and meet diverse biomedical requirements. Future advancements in materials science and biomedical engineering are anticipated to further optimize their efficacy and applicability in clinical settings. This review consolidates the current understanding and outlines future research directions for PLGA hydrogels, emphasizing their potential to revolutionize therapeutic delivery and improve patient outcomes.

14.
Exp Parasitol ; 265: 108811, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39111383

RESUMO

Alveolar echinococcosis (AE) is a severe disease caused by the infection with the larval stage of Echinococcus multilocularis, the metacestode. As there is no actual curative drug therapy, recommendations to manage AE patients are based on radical surgery and prophylactic administration of albendazole or mebendazole during 2 years to prevent relapses. There is an urgent need for new therapeutic strategies for the management of AE, as the drugs in use are only parasitostatic, and can induce toxicity. This study aimed at developing a drug delivery system for mefloquine, an antiparasitic compound which is highly active against E. multilocularis in vitro and in experimentally infected mice. We formulated mefloquine-loaded PLGA-PEG-COOH (poly-(lactic-co-glycolic acid)) nanoparticles that exhibit stable physical properties and mefloquine content. These nanoparticles crossed the outer acellular laminated layer of metacestodes in vitro and delivered their content to the inner germinal layer within less than 5 min. The in vitro anti-echinococcal activity of mefloquine was not altered during the formulation process. However, toxicity against hepatocytes was not reduced when compared to free mefloquine. Altogether, this study shows that mefloquine-loaded PLGA-PEG-COOH nanoparticles are promising candidates for drug delivery during AE treatment. However, strategies for direct parasite-specific targeting of these particles should be developed.


Assuntos
Echinococcus multilocularis , Mefloquina , Nanopartículas , Polietilenoglicóis , Animais , Mefloquina/farmacologia , Mefloquina/administração & dosagem , Echinococcus multilocularis/efeitos dos fármacos , Camundongos , Polietilenoglicóis/química , Nanopartículas/química , Equinococose/tratamento farmacológico , Sistemas de Liberação de Medicamentos , Feminino , Camundongos Endogâmicos BALB C , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Anti-Helmínticos/farmacologia , Anti-Helmínticos/administração & dosagem , Anti-Helmínticos/química , Humanos , Poliglactina 910
15.
Pharmaceutics ; 16(8)2024 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-39204436

RESUMO

Topical ocular drug delivery faces several challenges due to the eye's unique anatomy and physiology. Physiological barriers, tear turnover, and blinking hinder the penetration of drugs through the ocular mucosa. In this context, nanoparticles offer several advantages over traditional eye drops. Notably, they can improve drug solubility and bioavailability, allow for controlled and sustained drug release, and can be designed to specifically target ocular tissues, thus minimizing systemic exposure. This study successfully designed and optimized PLGA and PCL nanoparticles for delivering baricitinib (BTB) to the eye using a factorial design, specifically a three-factor at five-levels central rotatable composite 23+ star design. The nanoparticles were small in size so that they would not cause discomfort when applied to the eye. They exhibited low polydispersity, had a negative surface charge, and showed high entrapment efficiency in most of the optimized formulations. The Challenge Test assessed the microbiological safety of the nanoparticle formulations. An ex vivo permeation study through porcine cornea demonstrated that the nanoparticles enhanced the permeability coefficient of the drug more than 15-fold compared to a plain solution, resulting in drug retention in the tissue and providing a depot effect. Finally, the in vitro ocular tolerance studies showed no signs of irritancy, which was further confirmed by HET-CAM testing.

16.
Int J Pharm ; 663: 124556, 2024 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-39122196

RESUMO

Hot melt extrusion (HME) processed Poly (lactic-co-glycolic acid) (PLGA) implant is one of the commercialized drug delivery products, which has solid, well-designed shape and rigid structures that afford efficient locoregional drug delivery on the spot of interest for months. In general, there are a variety of material, processing, and physiological factors that impact the degradation rates of PLGA-based implants and concurrent drug release kinetics. The objective of this study was to investigate the impacts of PLGA's material characteristics on PLGA degradation and subsequent drug release behavior from the implants. Three model drugs (Dexamethasone, Carbamazepine, and Metformin hydrochloride) with different water solubility and property were formulated with different grades of PLGAs possessing distinct co-polymer ratios, molecular weights, end groups, and levels of residual monomer (high/ViatelTM and low/ ViatelTM Ultrapure). Physicochemical characterizations revealed that the plasticity of PLGA was inversely proportional to its molecular weight; moreover, the residual monomer could impose a plasticizing effect on PLGA, which increased its thermal plasticity and enhanced its thermal processability. Although the morphology and microstructure of the implants were affected by many factors, such as processing parameters, polymer and drug particle size and distribution, polymer properties and polymer-drug interactions, implants prepared with ViatelTM PLGA showed a smoother surface and a stronger PLGA-drug intimacy than the implants with ViatelTM Ultrapure PLGA, due to the higher plasticity of the ViatelTM PLGA. Subsequently, the implants with ViatelTM PLGA exhibited less burst release than implants with ViatelTM Ultrapure PLGA, however, their onset and progress of the lag and substantial release phases were shorter and faster than the ViatelTM Ultrapure PLGA-based implants, owing to the residual monomer accelerated the water diffusion and autocatalyzed PLGA hydrolysis. Even though the drug release profiles were also influenced by other factors, such as composition, drug properties and polymer-drug interaction, all three cases revealed that the residual monomer accelerated the swelling and degradation of PLGA and impaired the implant's integrity, which could negatively affect the subsequent drug release behavior and performance of the implants. These results provided insights to formulators on rational PLGA implant design and polymer selection.


Assuntos
Carbamazepina , Preparações de Ação Retardada , Dexametasona , Liberação Controlada de Fármacos , Tecnologia de Extrusão por Fusão a Quente , Metformina , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Solubilidade , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Dexametasona/química , Dexametasona/administração & dosagem , Metformina/química , Metformina/administração & dosagem , Preparações de Ação Retardada/química , Carbamazepina/química , Carbamazepina/administração & dosagem , Tecnologia de Extrusão por Fusão a Quente/métodos , Implantes de Medicamento/química , Ácido Poliglicólico/química , Portadores de Fármacos/química , Temperatura Alta , Ácido Láctico/química
17.
Children (Basel) ; 11(8)2024 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-39201877

RESUMO

Pediatric forearm fractures, particularly involving the shaft or diaphysis, are common injuries typically resulting from accidental trauma during various activities. Traditional treatment involves closed reduction and casting; however, surgical intervention may be necessary in certain cases. The gold standard surgical approach utilizes elastic stable intramedullary nailing (ESIN), but a newer technique uses bioabsorbable intramedullary nails made of poly(lactic-co-glycolic acid) (PLGA). This study aims to compare the outcomes of these two surgical methods in pediatric diaphyseal forearm fractures. We retrospectively reviewed 86 patients who underwent operative treatment due to the diaphyseal fractures of the forearm in the Surgical Division, Department of Pediatrics, Medical School, University of Pécs, Pécs, Hungary between 2018 and September 2022. The mean age was 9.48 (ranging from 4 to 17). A total of 41 patients underwent surgery with PLGA implants (RESIN technique), while 45 patients were treated with titanium elastic nails (ESIN technique). Various factors including patient demographics, injury mechanisms, fracture characteristics, and complications were assessed. Both groups showed similar gender distribution, with a majority of fractures occurring in boys (the male-female ratio was 31:10 in the PLGA group, while in the titanium elastic nailing (TEN) group, this ratio was 29:16, with no statistical difference between the groups (p > 0.005). The average age of the patients treated with PLGA implants (8.439 years) was lower compared to those treated with titanium nails (10.422 years). A statistically significant difference was found regarding the average age of the two groups (p = 0.0085). Left-sided injuries were more prevalent in both groups (59% of the cases in the PLGA group and 69% in the TEN group, with no statistically significant difference, p = 0.716), and fractures typically involved both the radius and ulna. This represents 93% of the cases in the PLGA group and 80% in the TEN group. Regarding the involvement of bones, we also did not find a statistically significant difference (p = 0.123). The mechanisms of injury predominantly involved indirect force, such as falls (30 cases in the PLGA group and 27 cases in the TEN group), and no statistically significant difference was found (p = 0.139) regarding the mechanism of the injury. Complication rates were lower in the PLGA group (7%) compared to the titanium group (20%). The treatment of pediatric diaphyseal forearm fractures using PLGA implants appears to be a viable alternative to traditional titanium implants. Advantages include no need for secondary surgery and associated cost savings and reduced complication rate and stress associated with anesthesia and surgery. Prospective randomized trials are warranted to further validate these findings and explore long-term outcomes.

18.
Adv Mater ; 36(36): e2401867, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39073167

RESUMO

Electro-reforming of poly(ethylene terephthalate) (PET) into valuable chemicals is garnering significant attention as it opens a mild avenue for waste resource utilization. However, achieving high activity and selectivity for valuable C2 products during ethylene glycol (EG) oxidation in PET hydrolysate on Pd electrocatalysts remains challenging. The strong interaction between Pd and carbonyl (*CO) intermediates leads to undesirable over-oxidation and poisoning of Pd sites, which hinders the highly efficient C2 products production. Herein, a nonmetallic alloying strategy is employed to fabricate a Pd-boron alloy aerogel (PdB), wherein B atoms are induced to regulate the electron structure and surface oxophilicity. This approach allows a remarkable mass activity of 6.71 A mgPd -1, glycolic acid (GA) Faradaic efficiency (FE) of 93.8%, and stable 100 h cyclic electrolysis. In situ experiments and density functional theory calculations reveal the contributions of B inserted in Pd lattice on highly effective EG-to-GA conversion. Interestingly, the heightened surface oxophilicity and regulated electronic structure by B incorporation weakened *CO intermediates adsorption and enhanced hydroxyl species affinity to accelerate oxidative *OH adspecies formation, thereby synergistically avoiding over-oxidation and boosting GA synthesis. This work provides valuable insights for the rational design of high-performance electrocatalysts for GA synthesis via an oxophilic B motifs incorporation strategy.

19.
J Cosmet Dermatol ; 2024 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-38979887

RESUMO

BACKGROUND: The hands are one of the areas where skin aging is most noticeable, alongside the face, but limited studies used dermoscopic evaluation on hand aging. The Dermoscopy Photoaging Scale (DPAS) is frequently used to assess face aging but is never used for hand aging. Treating skin aging using chemical peeling is a commonly used method to rejuvenate the skin on the hands, as it is relatively affordable. Using multiple chemical peels may yield more significant results. AIMS: To determine the effectiveness of a chemical peeling combination in retarding hand aging and to assess the utility of DPAS in this process. METHODS: This study involved 69 Fitzpatrick skin types III-IV volunteers aged 20-69. One hand of each participant was treated with 20% glycolic acid (GA), while the other received a combination of peels consisting of 20% GA and 15% trichloroacetic acid (TCA). The hands were clinically examined before and after the treatments, and dermoscopic examinations were performed using a modified DPAS. RESULTS: Four treatments improved clinical and dermoscopic characteristics in both hands. The combined peeling considerably improved pigmentation intensity on the dorsal hand compared to the GA peel (p < 0.001). Post-chemical peeling patient satisfaction increased significantly. CONCLUSIONS: The modified DPAS is a valuable instrument to assess the signs of hand aging. The combination of GA and TCA effectively improves skin aging of the hands and offers an accessible and economical option for addressing skin aging.

20.
J Indian Soc Periodontol ; 28(1): 79-83, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38988961

RESUMO

Background: Nonsurgical periodontal therapy results in the formation of a smear layer which inhibits tissue regeneration. Root biomodification (RB) using various agents has been tried for the enhancement of new attachment formation. However, no substantial therapeutic advantages of currently available root conditioning agents have been reported emphasizing the need for additional biologically acceptable agents. Glycolic acid (GA) due to its antimicrobial nature and ability of initiation and proliferation of fibroblasts may potentially modify root surface enabling regeneration. Materials and Methods: Eighty specimens from 40 single-rooted teeth were treated with 17% ethylenediaminetetraacetic acid (EDTA) and 5% GA and scanning electron microscopy analysis was done. The micrographs were examined for the evaluation of smear layer removal, total number of dentinal tubules, total number of patent dentinal tubules, mean diameter and surface area of dentinal tubules, and dentin erosion. Statistical analysis was done using unpaired t-test for intergroup comparison. Results: The efficacy of smear layer removal (P = 0.01) and dentin erosion (P = 0.042) was significantly better in the GA group. Both the groups showed no difference in dentinal tubule-related parameters. Conclusion: GA showed improved RB with greater smear layer removal and lesser dentin erosion, indicating its use as a potent alternative to the conventional EDTA root conditioning.

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